The purpose of this project is to investigate the regulation of liver growth and function by hormones and other factors. The isolated perfused rat liver is being used in these investigations. Since many of the pathways of amino acid utilization in liver are normally limited by the intracellular availability of these compounds, attempts are being made to characterize the transport systems for amino acids and to describe the role of hormones in the regulation of these processes. Studies during the past grant period demonstrate that an effect of growth hormone on amino acid transport may be a common mechanism in all of the effects of the hormone observed in the perfused liver. Other studies are being conducted to localize the effects of hormones and other factors on protein turnover to specific steps in the pathways of synthesis and degradation. Protein synthesis is inhibited in livers of diabetic animals as a result of a block in the initiation of peptide chains. This defect appears to result from a depletion of intracellular levels of amino acids rather than from a lack of insulin. The primary effect of insulin on protein turnover in liver appears to be on the degradative pathway.